BACKGROUND A previous dasatinib discontinuation (DADI) trial showed that 31 (49%) of 63 patients with chronic-phase chronic myeloid leukaemia who were treated with second-line or subsequent dasatinib could discontinue the drug safely. However, the safety and efficacy of discontinuing first-line dasatinib remains unclear. In this trial (the first-line DADI trial) we aimed to assess molecular relapse-free survival at 6 months after discontinuation of dasatinib in patients with chronic myeloid leukaemia who had been treated with first-line dasatinib and had maintained deep molecular response for at least 1 year. METHODS The first-line DADI trial was a single-arm, multicentre, phase 2 trial done at 23 hospitals in Japan. Patients with newly diagnosed chronic-phase chronic myeloid leukaemia without hepatosplenomegaly and extramedullary mass, who received at least 24-month dasatinib treatment and had a sustained deep molecular response (defined as BCR-ABL1/ABL1 international scale ≤0·0069% in at least four successive samples spanning a 12 month period) were enrolled. Other eligibility criteria were an age of 15 years or older, an Eastern Cooperative Oncology Group performance status score of 0-2, and no primary organ dysfunction. The primary outcome was molecular relapse-free survival (also known as treatment-free remission) after discontinuation of dasatinib at 6 months and was analysed in all patients who completed the 12-month consolidation phase. Safety was assessed in all patients who received treatment. This study closed early due to accrual and is registered with the UMIN Clinical Trials Registry (UMIN000011099). FINDINGS Between Sept 20, 2013 and July 12, 2016, 68 patients who had a deep molecular response after receiving first-line dasatinib for at least 24 months were enrolled and assigned to the consolidation phase. Nine patients were excluded during the consolidation phase and one patient was excluded after study completion because of meeting exclusion criteria. 58 patients discontinued dasatinib and were assessed. 32 (55%) of 58 patients had treatment-free remission at 6 months after dasatinib discontinuation, and median follow-up was 23·3 months (IQR 11·7-31·0). Treatment-free remission at 6 months was 55·2% (95% CI 43·7-69·6). No non-haematological adverse events worse than grade 2 occurred before dasatinib discontinuation. The most common haematological adverse event was anaemia (14 [21%] of 68 treated patients); three (4%) of 68 treated patients had grade 3 neutropenia and one (1%) had grade 4 lymphopenia. INTERPRETATION Our findings suggest that dasatinib could be safely discontinued after first-line treatment in patients with chronic myeloid leukaemia who had received at least 36 months of therapy and sustained deep molecular response; however, further confirmation in larger trials is needed. FUNDING Epidemiological and Clinical Research Information Network.

中文翻译：

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慢性粒细胞白血病患者在一线达沙替尼停药后的无治疗缓解（一线DADI试验）：单臂，多中心，2期试验。

背景技术先前的达沙替尼停药（DADI）试验显示，接受二线或随后的达沙替尼治疗的63例慢性期慢性髓样白血病患者中有31例（49％）可以安全地停药。但是，终止一线达沙替尼的安全性和疗效尚不清楚。在该试验（一线DADI试验）中，我们旨在评估在接受dasatinib一线治疗并在30天内维持深度分子应答的慢性粒细胞白血病患者停用dasatinib后6个月无分子复发的生存率。至少一年。方法DADI的一线试验是在日本的23家医院进行的单臂多中心2期试验。新诊断为慢性期慢性粒细胞白血病而无肝脾肿大和髓外肿块的患者，研究者接受了至少24个月达沙替尼治疗并持续持续的深分子应答（定义为BCR-ABL1 / ABL1国际标准，在至少12个为期12个月的连续时间内，至少有四个样本≤0·0069％）。其他符合条件的年龄为15岁或15岁以上，东部合作肿瘤小组的工作状态评分为0-2，并且没有原发性器官功能障碍。主要结果是达沙替尼停用6个月后无分子复发生存（也称为无治疗缓解），并且对完成12个月巩固期的所有患者进行了分析。评估所有接受治疗的患者的安全性。这项研究由于应募而提前结束，并已在UMIN临床试验注册中心（UMIN000011099）注册。发现在2013年9月20日至2016年7月12日之间，纳入一线达沙替尼至少24个月后具有深层分子反应的68位患者，并被分配到巩固期。在巩固阶段排除了9名患者，完成研究后排除了1名患者，因为符合排除标准。58例患者停用达沙替尼并接受评估。58例患者中有32例（55％）在达沙替尼停用后6个月无治疗缓解，中位随访时间为23·3个月（IQR 11·7-31·0）。6个月的无治疗缓解率为55·2％（95％CI 43·7-69·6）。在停用达沙替尼之前，没有发生任何非血液学不良事件，其不良反应不会超过2级。最常见的血液学不良事件是贫血（68位接受治疗的患者中有14位[21％]）；68名接受治疗的患者中有3名（4％）患有3级中性粒细胞减少症，而1名（1％）具有4级淋巴细胞减少症。解释我们的发现表明，对于接受了至少36个月的治疗并持续有深层分子反应的慢性粒细胞白血病患者，在一线治疗后可以安全地停用达沙替尼。但是，需要在更大的试验中进一步确认。资金流行病学和临床研究信息网络。